We have isolated and characterized a basic, heat-stable polypeptide growth factor from human serum that stimulates the replication of density inhibited Balb/c-3T3 cells, and density inhibited populations of diploid mouse or human fibroblasts. This highly purified polypeptide has a molecular weight of 1.3 x 10 to the 4th power daltons and isoelectric point of 9.7. The polypeptide has been labeled with 125I and an antiserum has been produced in a rabbit allowing the development of a specific, highly sensitive radioimmunoassay. Approximately 50 ng of this polypeptide are present in 1 ml of whole human serum as judged by radioimmunoassay. Studies in progress indicate that the human serum polypeptide growth factor derives largely from platelets. The growth factor is present in platelet-rich-plasma but not in platelet-poor-plasma as judged by both cell culture and radioimmunoassay. The growth factor polypeptide can be recovered from the platelets. Highly purified preparations of the growth factor have been obtained from outdated human platelets using cation exchange chromatography, gel filtration in 1 M acetic acid and isoelectric focusing. The immunologic and physicochemical properties of the purified human platelet growth factor are similar to those of the human serum factor. We propose the chemical characterization of the platelet growth polypeptide factor. The uptake and degradation of this polypeptide by normal and viral-transformed cells will be studied, and its presence in populations of human malignant cells grown in vitro will be quantitated by radioimmunoassay.